Iron metabolism in the body

Normally, the body of a healthy adult contains about 3-5 g of iron, thus, iron can be classified as a microelement. Iron is distributed unevenly in the body. Approximately 2/3 of iron is contained in the hemoglobin of red blood cells - this is the circulating fund (or pool) of iron. In adults, this pool is 2-2.5 g, in full-term newborns - 0.3-0.4 g, and in premature newborns - 0.1-0.2 g. Relatively much iron is contained in myoglobin: 0.1 g in men and 0.05-0.07 g in women. The human body contains more than 70 proteins and enzymes, which include iron (for example, transferrin, lactoferrin), the total amount of iron in them is 0.05-0.07 g. Iron transported by the transport protein transferrin makes up about 1% (iron transport fund). Iron reserves (depot, reserve fund), which make up about 1/3 of all iron in the human body, are extremely important for medical practice. The following organs perform the depot function:

• liver;
• spleen;
• bone marrow;
• brain.

Iron is contained in the depot in the form of ferritin. The amount of iron in the depot can be characterized by determining the concentration of SF. Today, SF is the only internationally recognized marker of iron reserves. The end product of iron metabolism is hemosiderin, which is deposited in tissues.

Iron is the most important cofactor of the enzymes of the mitochondrial respiratory chain, citrate cycle, DNA synthesis, it plays an important role in the binding and transport of oxygen by hemoglobin and myoglobin; proteins containing iron are necessary for the metabolism of collagen, catecholamines, tyrosine. Due to the catalytic action of iron in the reaction Fe ² * <--> Fe ³, free non-chelated iron forms hydroxyl radicals that can cause damage to cell membranes and cell death. In the process of evolution, protection from the damaging effect of free iron was solved by forming specialized molecules for the absorption of iron from food, its absorption, transport and deposition in a non-toxic soluble form. Transport and deposition of iron are carried out by special proteins: transferrin, transferrin receptor, ferritin. The synthesis of these proteins is regulated by a special mechanism and depends on the needs of the body.

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Iron metabolism in a healthy person is closed in a cycle

Every day, a person loses about 1 mg of iron with biological fluids and desquamated epithelium of the gastrointestinal tract. Exactly the same amount can be absorbed in the gastrointestinal tract from food. It should be clearly understood that iron enters the body only with food. Thus, every day 1 mg of iron is lost and 1 mg is absorbed. In the process of destruction of old erythrocytes, iron is released, which is utilized by macrophages and reused in the construction of heme. The body has a special mechanism for iron absorption, but it is excreted passively, that is, there is no physiological mechanism for iron excretion. Therefore, if the absorption of iron from food does not meet the needs of the body, iron deficiency occurs regardless of the cause.

Distribution of iron in the body

1. 70% of the total amount of iron in the body is part of hemoproteins; these are compounds in which iron is bound to porphyrin. The main representative of this group is hemoglobin (58% iron); in addition, this group includes myoglobin (8% iron), cytochromes, peroxidases, catalases (4% iron).
2. A group of nonheme enzymes - xanthine oxidase, NADH dehydrogenase, aconitase; these iron-containing enzymes are localized mainly in the mitochondria, play an important role in the process of oxidative phosphorylation, electron transport. They contain very little metal and do not affect the overall iron balance; however, their synthesis depends on the supply of iron to the tissues.
3. The transport form of iron is transferrin, lactoferrin, a low-molecular iron carrier. The main transport ferroprotein of plasma is transferrin. This protein of the beta-globulin fraction with a molecular weight of 86,000 has 2 active sites, each of which can attach one Fe ³⁺ atom. There are more iron-binding sites in plasma than iron atoms, and thus there is no free iron in it. Transferrin can also bind other metal ions - copper, manganese, chromium, but with different selectivity, and iron is bound primarily and more firmly. The main place of transferrin synthesis is liver cells. With an increase in the level of deposited iron in hepatocytes, transferrin synthesis is noticeably reduced. Transferrin, which carries iron, is avid for normocytes and reticulocytes, and the amount of metal absorption depends on the presence of free receptors on the surface of erythroid precursors. The reticulocyte membrane has significantly fewer binding sites for transferrin than the pronormocyte, meaning that iron uptake decreases as the erythroid cell ages. Low-molecular iron carriers provide intracellular iron transport.
4. Deposited, reserve or spare iron can be in two forms - ferritin and hemosiderin. The compound of reserve iron consists of the protein apoferritin, the molecules of which surround a large number of iron atoms. Ferritin is a brown compound, soluble in water, contains 20% iron. With excessive accumulation of iron in the body, the synthesis of ferritin increases sharply. Ferritin molecules are present in almost all cells, but there are especially many of them in the liver, spleen, bone marrow. Hemosiderin is present in tissues as a brown, granular, water-insoluble pigment. The iron content in hemosiderin is higher than in ferritin - 40%. The damaging effect of hemosiderin in tissues is associated with damage to lysosomes, accumulation of free radicals, which leads to cell death. In a healthy person, 70% of the reserve iron is in the form of ferritin, and 30% in the form of hemosiderin. The rate of hemosiderin utilization is significantly lower than that of ferritin. Iron reserves in tissues can be assessed based on histochemical studies using a semi-quantitative assessment method. The number of sideroblasts is counted - nuclear erythroid cells containing different amounts of non-heme iron granules. The peculiarity of iron distribution in the body of young children is that they have a higher iron content in erythroid cells and less iron in muscle tissue.

Iron balance regulation is based on the principles of almost complete reutilization of endogenous iron and maintenance of the required level due to absorption in the gastrointestinal tract. The half-life of iron excretion is 4-6 years.

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Iron absorption

Absorption occurs mainly in the duodenum and the initial section of the jejunum. In case of iron deficiency in the body, the absorption zone extends in the distal direction. The daily diet usually contains about 10-20 mg of iron, but only 1-2 mg is absorbed in the gastrointestinal tract. The absorption of heme iron significantly exceeds the intake of inorganic iron. There is no clear opinion regarding the effect of iron valence on its absorption in the gastrointestinal tract. V. I. Nikulicheva (1993) believes that Fe ²⁺ is practically not absorbed either at normal or at excess concentrations. According to other authors, iron absorption does not depend on its valence. It has been established that the decisive factor is not the valence of iron, but its solubility in the duodenum at an alkaline reaction. Gastric juice and hydrochloric acid participate in the absorption of iron, ensure the restoration of the oxide form (Fe ^H ) to the oxide form (Fe ²⁺ ), ionization, and the formation of components available for absorption, but this applies only to non-heme iron and is not the main mechanism for regulating absorption.

The process of absorption of heme iron does not depend on gastric secretion. Heme iron is absorbed in the form of a porphyrin structure and only in the intestinal mucosa does it split off from heme and form ionized iron. Iron is better absorbed from meat products (9-22%) containing heme iron, and much worse from plant products (0.4-5%), which contain non-heme iron. Iron is absorbed from meat products in different ways: iron is absorbed worse from the liver than from meat, since iron in the liver is contained in the form of hemosiderin and ferritin. Boiling vegetables in a large amount of water can reduce the iron content by 20 %.

The absorption of iron from breast milk is unique, although its content is low - 1.5 mg / l. In addition, breast milk increases the absorption of iron from other products consumed simultaneously with it.

During digestion, iron enters the enterocyte, from where it passes into the blood plasma along the concentration gradient. When there is a deficiency of iron in the body, its transfer from the lumen of the gastrointestinal tract to the plasma accelerates. When there is an excess of iron in the body, the bulk of the iron is retained in the cells of the intestinal mucosa. The enterocyte, loaded with iron, moves from the base to the top of the villus and is lost with the desquamated epithelium, which prevents excess metal from entering the body.

The process of iron absorption in the gastrointestinal tract is influenced by various factors. The presence of oxalates, phytates, phosphates, and tannin in poultry reduces iron absorption, as these substances form complexes with iron and remove it from the body. On the contrary, ascorbic, succinic, and pyruvic acids, fructose, sorbitol, and alcohol enhance iron absorption.

In plasma, iron binds to its carrier, transferrin. This protein transports iron primarily to the bone marrow, where iron penetrates into erythrocytes, and transferrin returns to the plasma. Iron enters the mitochondria, where heme synthesis occurs.

The further path of iron from the bone marrow can be described as follows: during physiological hemolysis, 15-20 mg of iron per day is released from erythrocytes, which is utilized by phagocytic macrophages; then the main part of it again goes to the synthesis of hemoglobin and only a small amount remains in the form of reserve iron in macrophages.

30% of the total iron content in the body is not used for erythropoiesis, but is deposited in depots. Iron in the form of ferritin and hemosiderin is stored in parenchymatous cells, mainly in the liver and spleen. Unlike macrophages, parenchymatous cells consume iron very slowly. Iron intake by parenchymatous cells increases with significant iron excess in the body, hemolytic anemia, aplastic anemia, renal failure and decreases with severe metal deficiency. Iron release from these cells increases with bleeding and decreases with blood transfusions.

The overall picture of iron metabolism in the body will be incomplete if we do not take into account tissue iron. The amount of iron that is part of ferroenzymes is small - only 125 mg, but the importance of tissue respiration enzymes is difficult to overestimate: without them, the life of any cell would be impossible. The iron reserve in cells allows us to avoid direct dependence of the synthesis of iron-containing enzymes on fluctuations in its intake and expenditure in the body.

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Physiological losses and features of iron metabolism

Physiological iron losses from the body of an adult are about 1 mg per day. Iron is lost with exfoliating skin epithelium, epidermal appendages, sweat, urine, feces, and exfoliating intestinal epithelium. In women, iron is also lost with blood during menstruation, pregnancy, childbirth, and lactation, which is about 800-1000 mg. Iron metabolism in the body is shown in diagram 3. It is interesting to note that the iron content in the serum and transferrin saturation change during the day. High iron concentrations in the serum are observed in the morning and low values in the evening. Sleep deprivation in people leads to a gradual decrease in the iron content in the serum.

Iron metabolism in the body is influenced by trace elements: copper, cobalt, manganese, nickel. Copper is necessary for the absorption and transport of iron; its effect is realized through cytochrome oxidase, ceruloplasmin. The effect of manganese on the process of hematopoiesis is non-specific and is associated with its high oxidizing capacity.

To understand why iron deficiency is most common in young children, adolescent girls, and women of childbearing age, let's look at the characteristics of iron metabolism in these groups.

Iron accumulation in the fetus occurs throughout pregnancy, but most intensively (40%) in the last trimester. Therefore, prematurity of 1-2 months leads to a reduction in iron supply by 1.5-2 times compared to full-term children. It is known that the fetus has a positive iron balance, going against the concentration gradient in favor of the fetus. The placenta more intensively captures iron than the bone marrow of the pregnant woman, and has the ability to absorb iron from the mother's hemoglobin.

There are conflicting data on the effect of maternal iron deficiency on fetal iron stores. Some authors believe that sideropenia in pregnancy does not affect fetal iron stores; others believe that there is a direct relationship. It can be assumed that a decrease in the iron content of the mother's body leads to a deficiency of iron stores in the newborn. However, the development of iron deficiency anemia due to congenital iron deficiency is unlikely, since the incidence of iron deficiency anemia, hemoglobin levels, and serum iron in the first day after birth and in the following 3-6 months do not differ in children born to healthy mothers and mothers with iron deficiency anemia. The iron content in the body of a full-term and premature newborn is 75 mg/kg.

In children, unlike adults, alimentary iron must not only replenish the physiological losses of this microelement, but also meet growth needs, which is on average 0.5 mg/kg per day.

Thus, the main prerequisites for the development of iron deficiency in premature babies, children from multiple pregnancies, and children under 3 years of age are:

• rapid depletion of reserves due to insufficient exogenous iron intake;
• increased need for iron.

Iron metabolism in adolescents

A feature of iron metabolism in adolescents, especially girls, is a pronounced discrepancy between the increased need for this microelement and its low intake into the body. The reasons for this discrepancy are: rapid growth, poor nutrition, sports activities, heavy menstruation, and an initial low iron level.

In women of childbearing age, the main factors leading to the development of iron deficiency in the body are heavy and prolonged menstruation, multiple pregnancies. The daily iron requirement for women who lose 30-40 ml of blood during menstruation is 1.5-1.7 mg/day. With greater blood loss, the iron requirement increases to 2.5-3 mg/day. In fact, only 1.8-2 mg/day can enter through the gastrointestinal tract, that is, 0.5-1 mg/day of iron cannot be replenished. Thus, the microelement deficiency will be 15-20 mg per month, 180-240 mg per year, 1.8-2.4 g per 10 years, that is, this deficiency exceeds the content of reserve iron in the body. In addition, the number of pregnancies, the interval between them, and the duration of lactation are important for the development of iron deficiency in a woman.